Principles of General Anaesthesia Flashcards
What are the five clinically desirable effects of general anaesthetics? State which two effects are caused by ALL general anaesthetics.
Loss of consciousness (ALL) Suppression of reflex responses (ALL) Relief of pain Muscle relaxation Amnesia CRAMP (consciousness, reflex, amnesia, muscle, pain)
Name 4 inhalational general anaesthetics.
Nitrous oxide
Diethyl ether
Halothane
Enflurane
Name 2 IV general anaesthetics.
Propofol
Etomidate
What is the Meyer/Overton correlation?
For a long time it was believed that anaesthetic potency increases in direct proportion with the oil/gas partition coefficient
In other words: anaesthetic potency is directly correlated with lipid solubility
hat was the explanation for the Meyer/Overton correlation?
The drugs disturbed the lipid bilayer
What were the problems with this explanation?
At therapeutic doses, the changes to the lipid bilayer were minute
How would the change in membrane impact on membrane proteins anyway?
What are the two real mechanisms of action of general anaesthetics?
Reduced neuronal excitability
Altered synaptic function
Describe the difference in the selectivity of IV and inhalational agents.
IV agents are more selective for GABA-A
Inhalational agents are far less selective
Which specific subunits of the GABA-A receptor do IV act on, where are they and what are the effects
GABA receptors with a lot of Beta 3 subunits– brainstem/spinal cord, activation causes reflex suppression
GABA receptors with a lot of Alpha 5 subunits – hippocampus, activation causes amnesia
Which subunit of the GABA-A receptor do inhalational agents seem to be more selective for?
Alpha 1 – important in suppression of reflex responses
Explain how nitrous oxide induces its anaesthetic effect.
Nitrous oxide competes for the glycine-binding site on NMDA receptors (excitatory glutamate receptors)
Glycine is an important coagonist of NMDA receptors – it allows the full receptor response to be transduced. Nitroux oxide competes with this, less NMDA activation =less excitation
What is the effect of blocking neuronal nicotinic acetylcholinereceptors with regards to general anaesthesia?
Blocking nAChR leads to reduced nerve conduction
This is important for amnesia and relief of pain
Which channels are important in reducing neuronal excitability via the action of inhalational agents?
TREK – background leak K+ channels
These lead to hyperpolarisation of neurones and inhalational agents facilitate the opening of these channels
Inhalational agents are less selective than IV agents. What effect does this have on the dose needed to induce general anaesthesia?
Generally speaking, a higher dose of inhalational agents is required
Explain how general anaesthetics cause a loss of consciousness.
Loss of consciousness is caused by depressing the excitability of thalamocortical neurones AND suppression of neurons within the RAS (normally involved in maintaining consciousness)
This is mediated by TREK channels and GABA-A
Explain how general anaesthetics suppress reflex responses.
Depression of reflex pathways in the dorsal horn of the spinal cord
This is done by anaesthetics that enhance GABA-A and glycine function (glycine receptors are ionotropic receptors that facilitate Cl- influx)
Explain how general anaesthetics cause amnesia.
There are a lot of GABA-A receptors in the hippocampus that have the alpha 5 subunit
General anaesthetics stimulate these receptors to decrease synaptic transmission in the hippocampus
Explain how blood: gas partition coefficient affects the speed at which the general anaesthetic penetrates the brain.
If you have a GA that dissolves really well in the blood, then there is less GA in the gas phase in blood and hence less GA penetrates the blood-brain barrier and reaches the brain
It is only anaesthetic that remains in the gas phase that diffuses easily into the brain
Would a general anaesthetics with a high or low blood: gas partition coefficient be useful for anaesthetics and why?
LOW
This means that less of the GA will dissolve in the blood so more will be left in the gas phase
Hence more of the drug will penetrate the blood-brain barrier and reach the brain
What are the benefits of inhalation anaesthetics?
Rapidly eliminated
Good control of the depth of anaesthesia
What are the benefits of IV anaesthetics?
Fast induction
Less coughing/excitatory phenomena
What types of drugs can be used to achieve:
a. Relief of pain
b. Muscle relaxation
c. Amnesia
a. Relief of pain Opioids b. Muscle relaxation Neuromuscular blockers c. Amnesia Benzodiazepines
Summarise the MOA of IV and Inhalational GA agents
IV - very specific for GABAa receptors (beta 3 and alpha 5 subunits)
Inhalational- very non specific, wide range of MOA including:
- enhance GABAa action (especially ones containing alpha 3 subunits)
- activate TREK channels (background leak K+ channels) and causing hyperpolarisation and hence reduced neuronal excitability
- block neuronal nicotinic AChR - analgesic effect
- Blocks NMDA receptors eg Nitrous oxide
